The role of c-myc has been well-studied in gene regulation and oncogenesis but remains elusive in murine development from midgestation. We determined c-myc function during kidney development, organogenesis, and homeostasis by conditional loss of c-myc induced at two distinct phases of nephrogenesis, embryonic day (e) 11.5 and e17.5. Deletion of c-myc in early metanephric mesenchyme (e11.5) led to renal hypoplasia from e15.5 to e17.5 that was sustained until adulthood (range, 20-25%) and, hence, reproduced the human pathologic condition of renal hypoplasia. This phenotype resulted from depletion of c-myc-positive cells in cap mesenchyme, causing a approximately 35% marked decrease of Six2- and Cited1-stem/progenitor population and of proliferation that likely impaired self-renewal. By contrast, c-myc loss from e17.5 onward had no impact on late renal differentiation/maturation and/or homeostasis, providing evidence that c-myc is dispensable during these phases. This study identified c-myc as a modulator of renal organogenesis through regulation of stem/progenitor cell population.